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Aspirin Resistance: Do we have standardized methods for measurement?

Linda Leav, Pharm.D. Candidate (2006)*
Edith A. Nutescu, Pharm.D.
September, 2005

Historically, the term "aspirin resistance" has been used to describe patients who experience an arterial thromboembolic event despite being treated with aspirin. Although there is no standardized definition of aspirin resistance, it can be characterized clinically and pharmacodynamically. Clinically, aspirin resistance occurs when there is a vascular event despite thromboprophylaxis with aspirin. In contrast, the pharmacodynamic aspect of aspirin resistance is identified as the ineffectiveness of the antiplatelet property of aspirin, resulting in less reduction in platelet aggregation.1 Various mechanisms of aspirin resistance have been proposed. 2 [Table 1]

TABLE 1: Possible mechanisms of aspirin "resistance"
This table is available with the full text of the article on the publisher's website at http://www.blackwell-synergy.com/doi/full/10.1111/j.1538-7836.2005.01351.x. The table is from reference 2.

Despite various commercial tests available to test for aspirin resistance, to date a clinically validated and uniformly accepted test to assess the effect of aspirin on platelet aggregation is lacking. 1 Historically, the method of choice for testing platelet function has involved in vitro platelet aggregation studies using the method of Born. 4 These traditional studies are performed using platelet-rich plasma and platelet aggregation is determined by using optical platelet aggregometers. Aggregation is usually induced by adding a platelet agonist (i.e. ADP, arachidonic acid, collagen, epinephrine) to the platelet rich plasma. The amount of platelet aggregation is related to the amount of light that passes through the solution, and the results are reported in units of percentage of light transmission on a scale of 0-100%. The performance of this assay is cumbersome, and it requires a specialized laboratory setting. 2

More recently various whole blood, point of care analyzers have become commercially available including the Platelet Function Analyzer 100 (PFA-100®), Impact®, and the VerifyNow® aspirin assay. These devices are less cumbersome and more convenient to use compared to the traditional tests using the optical method. 5 The PFA-100 analyzer functions by aspirating a blood sample through a capillary tube and through a small slit aperture cut into a membrane coated with collagen-epinephrine or collagen-ADP. The closure time in seconds for a platelet plug to occlude the slit aperture is inversely related to platelet activity. A value of 193 or less is considered normal, and values greater than 300 are considered non-closure. This analyzer is a convenient tool for measuring platelet aggregation, but its role in measuring aspirin resistance has not been appropriately evaluated. 1, 3, 5 The VerifyNow Aspirin Assay detects platelet aggregation based on agglutination of platelets on fibrinogen-coated beads detected by an optical turbidimetry method. Results are expressed in aspirin response units with a value of 550 or more defined as aspirin resistance. 1, 5 Table 2 summarizes the features of various tests used for testing aspirin resistance. Table 2, which is from reference 2, is available along with the full text of the article on the publisher's website at http://www.blackwell-synergy.com/doi/full/10.1111/j.1538-7836.2005.01351.x.

Aspirin resistance can be a major health issue, potentially increasing the number of vascular events in patients on aspirin therapy. Even though there are different laboratory tools that can be used to analyze the antiplatelet effects of aspirin, more work is needed to standardize and validate these tests. In addition, the treatment for aspirin resistance is controversial and not standardized, although most healthcare providers will address the issue by altering patients' current therapy. As more research is being focused on this issue, testing for aspirin resistance can be used to help detect patients that may be at risk or have some degree of resistance and to possibly initiate alternative therapies.

References

  1. Martin CP, Talbert RL. Aspirin resistance: an evaluation of current evidence and measurement methods. Pharmacotherapy 2005;25(7):942-53.

  2. Michelson AD, Cattaneo M, Eikelboom JW, Gurbel P, Kottke-Marchant K, Kunicki TJ, et al. Aspirin resistance: position paper of the working group on aspirin resistance. J Thromb Haemost 2005;3(6):1309-11.

  3. Dyszkiewicz-Korpanty AM, Frenkel EP, Sarode R. Approach to the assessment of platelet function: comparison between optical-based platelet-rich plasma and impedance-based whole blood platelet aggregation methods. Clin Appl Thomb Hemost 2005;11(1):25-35.

  4. Helgason CM, Bolin KM, Hoff JA, et.al. Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994;25:2331-6.

  5. Michelson AD. Platelet function testing in cardiovascular diseases [online exclusive article]. Circulation 2004;110:e489-93. Available from http://circ.ahajournals.org/cgi/reprint/110/19/e489.

*Linda Leav, Pharm.D. Candidate (2006)
ClotCare Guest Editor
The University of Illinois at Chicago
College of Pharmacy

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Sunday, December 17, 2017